Hydrocortisone and semi-synthetic analogs, such as methyl prednisolone and dexamethasone, have been extensively used in prevention and therapy of different forms of shock, as for instance: (a) septic shock and subsequent abdominal infarction, at a dose of 25-30 mg/Kg, W. Schumer, Ann. Surg. 184,333 (1976), or acute peritonitis (post-operative or from appendicitis, perforated gastrointestinal ulcer, intestinal occlusion, enteritis, neoplastic perforation of colon and other causes) complicated by endotoxin shock, P. Stefanini, V. Speranza, Postgrad. Med. J. 43,79 (1967); (b) shock from burns at a booster dose of 2-3 gr. of hydrocorisone or equivalent doses of other semi-synthetic steroids, M. O. Chiaradia, B. Gagliardi, G. C. Serra, Arch. Osp. Mare 20,432 (1968); and (c) traumatic shock, at 50 mg/Kg associated with low molecular weight dextran (LMWD) at 2 gr/Kg, G. C. Serra, M. Simone, Acta Anesthes. 16, suppl., 195 (1965).
The actions of hydrocortisone in shock, specifically endotoxin-shock, can be summarized as follows: blockage of adrenergic receptors; "permissive" action, i.e., normalization of the effects of catecholamines on arteriolocapillary bed; increase of capillary resistance; and endotoxin-specific antitoxic activity.
Glucocorticoid therapy in shock prevention and therapy must be associated with other therapeutic agents, such as plasma volume expanders (dextrans), antibiotics, Aprotinin (protease inhibitor), alpha-adrenergic blocking agents (phenoxybenzamine) or, as an alternative, pressor agents (Levarterenol or Metaraminol). In shock therapy the recommended dosage for hydrocortisone is at least 300 mg; see Goodman and Gilman, "The Pharmacological Basis of Therapeutics" 5th Ed., pg. 1501 (1975). Due to the very low solubility in water of the bases--as an example at 25.degree. C., only 280 mg hydrocortisone base dissolves in 1000 ml water--hydrocortisone and methylprednisolone hydrosoluble derivatives, typically sodium hemisuccinates or sodium phosphates, must be administered by injection. Unfortunately, these derivatives are less active than the bases, and consequently larger amounts must be administered, i.e., up to 2-10 gr, to achieve a therapeutic effect. The administration of such a large amount of one single steroid impairs the physiological hormonal equilibrium and produces unwanted side effects.